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Phase 1 Study of Oral TP-1454

Primary Purpose

Advanced Solid Tumor, Anal Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TP-1454 monotherapy
Sponsored by
Sumitomo Pharma America, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring Sumitomo Pharma Oncology, Phase 1, Advanced Solid Tumors, Refractory, Anal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Dose Escalation: Have a histologically confirmed diagnosis of a) advanced metastatic or progressive solid tumor, who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition (Monotherapy Arm) b) advanced/metastatic renal cell carcinoma (RCC) and patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC), who are eligible per FDA approval of ipilimumab and nivolumab by indication for the protocol- defined regimen (combination arm).
  2. Dose Expansion: Have a histologically confirmed diagnosis of mNSCLC expressing PD-L1 (≥1% as determined by an FDA-approved test) with no EGFR or ALK genomic tumor aberrations, and who are eligible per FDA approval of ipilimumab and nivolumab by indication for the protocol-defined regimen
  3. Naïve to prior treatment with any PD1 or CTLA-4 inhibitor (Combination Arm Only)
  4. Have measurable as outlined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
  6. Have a life expectancy ≥3 months
  7. Be ≥18 years of age
  8. Have a negative pregnancy test (if female of childbearing potential)
  9. Have acceptable liver function:

    1. Bilirubin ≤1.5x upper limit of normal (ULN) (unless associated with Gilbert syndrome)
    2. Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤2.5x ULN* *If liver metastases are present, then ≤ 3x ULN is allowed. ** For patients who will receive ipilimumab and nivolumab in combination with TP-1454 then ≤ 3X ULN is allowed
  10. Have acceptable renal function: calculated creatinine clearance ≥30 mL/min (using Cockcroft Gault formula)
  11. Have acceptable hematologic status:

    1. Granulocyte ≥1500 cells/mm3
    2. Platelet count ≥100,000 (plt/mm3)
    3. Hemoglobin ≥8 g/dL
  12. Have acceptable coagulation status:

    1. Prothrombin time (PT) within 1.5x normal limits
    2. Activated partial thromboplastin time (aPTT) within 1.5x normal limits
  13. Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation and for at least 3 months (males) and 6 months (females) after the last study drug dose.

    Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

  14. Have read and signed the Institutional Review Board (IRB)-approved informed consent form (ICF) prior to any study-related procedure. (In the event that the patient is rescreened for study participation or a protocol amendment alters the care of an ongoing patient, a new ICF must be signed.)

Exclusion Criteria:

  1. New York Heart Association Class III or IV cardiac disease, or myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, congestive heart failure within the past 6 months or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1/Day 1
  2. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450 msec in men and >470 msec in women
  3. Have a seizure disorder requiring anticonvulsant therapy
  4. Have untreated central nervous system (CNS) metastases including carcinomatous meningitis. Patients with definitively treated (radiotherapy or surgery) CNS metastases may be eligible if asymptomatic and not receiving corticosteroids in excess of prednisone 10 mg (or equivalent) per day for ≥2 weeks before first dose of TP-1454
  5. Have hypoxemia (defined as resting O2 saturation of ≤90% breathing room air)
  6. Have symptomatic interstitial lung disease or radiographic changes in the lungs that may make detection, diagnosis, or treatment of drug-induced pneumonitis difficult
  7. Have undergone major surgery within 2 weeks prior to Cycle 1/Day 1
  8. Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  9. Are pregnant or nursing
  10. Received treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 28 days or 5 half-lives, whichever occurs first, prior to study entry (6 weeks for nitrosoureas or mitomycin C)
  11. Are unwilling or unable to comply with procedures required in this protocol
  12. Have known infection with human immunodeficiency virus, hepatitis B, or hepatitis C. Patients with history of chronic hepatitis that is currently not active are eligible
  13. Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
  14. Are currently receiving any other investigational agent
  15. Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation
  16. Have malabsorption conditions (eg, Crohn's disease, etc) or have undergone significant surgery to the gastrointestinal tract that could impair absorption or that could result in short bowel syndrome with diarrhea due to malabsorption
  17. Require systemic corticosteroids greater than the equivalent of 10mg of prednisone or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (e.g., cyclosporine or methotrexate) (patients receiving combination therapy only)
  18. Have a history of malignancy within the past 24 months except curatively treated in situ cancers
  19. Have active, known, or suspected autoimmune disease with the exception of (patients receiving combination therapy only):

    • Type I diabetes mellitus
    • Hypothyroidism only requiring hormone replacement
    • Skin disorders not requiring systemic treatment, eg, vitiligo, alopecia, or psoriasis
  20. Have known EGFR mutations or ALK alterations that are sensitive to targeted therapy in NSCLC tumor types (patients receiving combination therapy only)
  21. Have ≥Grade 2 peripheral neuropathy (patients receiving combination therapy only)

Sites / Locations

  • Mayo Clinic ArizonaRecruiting
  • University of Southern California - Norris Cancer Center and Hoag Memorial HospitalRecruiting
  • Mayo Clinic JacksonvilleRecruiting
  • Mayo Clinic RochesterRecruiting
  • Comprehensive Cancer Center of NevadaRecruiting
  • Vanderbilt UniversityRecruiting
  • Texas Oncology Baylor Sammons Cancer Center
  • Huntsman Cancer InstituteRecruiting
  • University of Virginia
  • Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TP-1454

Arm Description

Flat dose once or twice daily

Outcomes

Primary Outcome Measures

Determine maximum tolerated dose (MTD)
MTD will be determined based upon toxicity grades which are defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
Determine recommended Ph2 dose (RP2D) of TP-1454
To establish the RP2D for future studies with TP-1454. MTD, PK and PD data to be reviewed.

Secondary Outcome Measures

Determine incidence of dose-limiting toxicities (DLTs)
A DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days
Determine antitumor activity of TP-1454.
Objective radiographic assessment to be performed to determine antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST criteria v 1.1).

Full Information

First Posted
March 20, 2020
Last Updated
October 2, 2023
Sponsor
Sumitomo Pharma America, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04328740
Brief Title
Phase 1 Study of Oral TP-1454
Official Title
A Phase I, First-in-human, Open-label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP 1454
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 8, 2020 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sumitomo Pharma America, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will evaluate the safety and tolerability of oral TP-1454 in patients with advanced metastatic or progressive solid tumors and anal cancer.
Detailed Description
Primary Objective: • To establish the MTD and/or Recommended Phase 2 Dose (RP2D) of orally administered TP-1454 in patients with metastatic solid tumors and anal cancer. Secondary Objectives: To establish the pharmacokinetic (PK) profile of orally administered TP-1454 To observe patients for any evidence of antitumor activity of TP 1454 by objective radiographic assessment To assess the safety and tolerability of TP-1454

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor, Anal Cancer
Keywords
Sumitomo Pharma Oncology, Phase 1, Advanced Solid Tumors, Refractory, Anal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Open label
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TP-1454
Arm Type
Experimental
Arm Description
Flat dose once or twice daily
Intervention Type
Drug
Intervention Name(s)
TP-1454 monotherapy
Intervention Description
Flat dose once or twice daily, alone
Primary Outcome Measure Information:
Title
Determine maximum tolerated dose (MTD)
Description
MTD will be determined based upon toxicity grades which are defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
Time Frame
50 months
Title
Determine recommended Ph2 dose (RP2D) of TP-1454
Description
To establish the RP2D for future studies with TP-1454. MTD, PK and PD data to be reviewed.
Time Frame
50 months
Secondary Outcome Measure Information:
Title
Determine incidence of dose-limiting toxicities (DLTs)
Description
A DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days
Time Frame
28 days
Title
Determine antitumor activity of TP-1454.
Description
Objective radiographic assessment to be performed to determine antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST criteria v 1.1).
Time Frame
50 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients to be enrolled during Dose Escalation with capsules must have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition (enrollment complete). Following approval of Amendment 5.0, patients to be enrolled during Dose Escalation with Tablets must have a histologically confirmed diagnosis of anal cancer and: have received at least one line of systemic platinum-based therapy in the advanced setting; (Note: Systemic platinum therapy given in the adjuvant setting will meet this criterion if there is recurrence or metastasis within 6 months of completing adjuvant therapy.); and have received no more than 3 total lines of systemic therapy in the advanced setting. Have measurable disease as outlined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Be ≥18 years of age Have a negative pregnancy test (if female of childbearing potential) Have acceptable liver function: Bilirubin ≤1.5x upper limit of normal (ULN) (unless associated with Gilbert syndrome) Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤2.5x ULN* *If liver metastases are present, then ≤ 3x ULN is allowed. Have acceptable renal function: calculated creatinine clearance ≥60 mL/min (using Cockcroft Gault formula) Have acceptable hematologic status: Granulocyte ≥1500 cells/mm3 Platelet count ≥100,000 (plt/mm3) Hemoglobin ≥8 g/dL Have acceptable coagulation status: International Normalized Ratio (INR) or Prothrombin time (PT) within 1.5x normal limits unless the patient is receiving anticoagulant therapy, in which case, the patient's PT or partial thromboplastin time (PTT) must be within the therapeutic range of intended use for their anticoagulant. Partial activated partial thromboplastin time (aPTT) or activated partial thromboplastin time (aPTT) within 1.5x normal limits unless the patient is receiving anticoagulant therapy, in which case, the patient's PT or PTT must be within the therapeutic range of intended use for their anticoagulant. Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use a highly effective method of contraception prior to study entry for the duration of study participation and for at least 3 months (males) and 6 months (females) after the last study drug dose. Male patients only: must agree not to donate sperm during the study and for 3 months after the last dose of TP-1454. Women of childbearing potential must agree not to donate eggs during the study and for 6 months after the last dose of TP-1454. Have read and signed the Institutional Review Board (IRB)-approved informed consent form (ICF) prior to any study-related procedure. (In the event that the patient is rescreened for study participation or a protocol amendment alters the care of an ongoing patient, a new ICF must be signed.) Dose escalation in mSCCA with tablets only: Patients who are HIV+ may be enrolled if the following conditions are met: CD4+ T-cell count ≥ 300/µL No opportunistic infection within the past 12 months Treatment with established antiretroviral therapy for at least 4 weeks with a viral load < 400 copies/mL prior to first dose with TP-1454. Dose escalation in mSCCA with tablets only: Patients who have had hepatitis B or C viral infections (HBV or HCV, respectively) may be enrolled if the following conditions are met: Have completed or are undergoing curative antiviral treatment with viral load below the limit of quantification Test positive for antibody and negative for viral RNA Exclusion Criteria: New York Heart Association Class III or IV cardiac disease, or myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, congestive heart failure within the past 6 months or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1/Day 1 Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450 msec in men and >470 msec in women Have a seizure disorder requiring anticonvulsant therapy Have untreated central nervous system (CNS) metastases including carcinomatous meningitis. Patients with definitively treated (radiotherapy or surgery) CNS metastases may be eligible if asymptomatic and not receiving corticosteroids in excess of prednisone 10 mg (or equivalent) per day for ≥2 weeks before first dose of TP-1454 Have hypoxemia (defined as resting O2 saturation of ≤90% breathing room air) Have symptomatic interstitial lung disease Have undergone major surgery within 2 weeks prior to Cycle 1/Day 1 Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy Are pregnant or nursing Received treatment with radiation therapy to a target lesion, surgery, chemotherapy, or investigational therapy within 28 days or 5 half-lives, whichever occurs first, prior to study entry (6 weeks for nitrosoureas or mitomycin C) Are unwilling or unable to comply with procedures required in this protocol Dose escalation in solid tumors with capsules only: Have known infection with hepatitis B, or hepatitis C. Patients with history of chronic hepatitis that is currently not active are eligible Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor Are currently receiving any other investigational agent Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation(s) Have malabsorption conditions or have undergone significant surgery to the gastrointestinal tract that could impair absorption or that could result in short bowel syndrome with diarrhea due to malabsorption Have a history of malignancy within the past 24 months except curatively treated in situ cancers
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Holly Beever, RN
Phone
210-365-9014
Email
holly.beever@us.sumitomo-pharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Susan Smith, MSN
Phone
210-414-7702
Email
susan.smith@us.sumitomo-pharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jian Li, MD
Organizational Affiliation
Sumitomo Pharma America, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Wu
First Name & Middle Initial & Last Name & Degree
Thai Ho, MD
Facility Name
University of Southern California - Norris Cancer Center and Hoag Memorial Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033 and 92663
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anthony El-Khoueiry, MD
First Name & Middle Initial & Last Name & Degree
Anthony El-Khoueiry, MD
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Umair Majeed
First Name & Middle Initial & Last Name & Degree
Hani Babiker, MD
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhaohui Jin, MD
First Name & Middle Initial & Last Name & Degree
Zhaohui Jin, MD
Facility Name
Comprehensive Cancer Center of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grzegorz Obara, MD
First Name & Middle Initial & Last Name & Degree
Grzegorz Obara, MD
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cathy Eng, MD
First Name & Middle Initial & Last Name & Degree
Cathy Eng, MD
Facility Name
Texas Oncology Baylor Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Completed
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ignacio Garrido-Laguna, MD, PhD
First Name & Middle Initial & Last Name & Degree
Ignacio Garrido-Laguna, MD, PhD
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Individual Site Status
Completed
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ariel Nelson, MD
First Name & Middle Initial & Last Name & Degree
Ariel Nelson, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Phase 1 Study of Oral TP-1454

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